Effects of Prophylactic Foscarnet on Human Herpesvirus-6 Reactivation and Encephalitis in Cord Blood Transplant Recipients: A Prospective Multicenter Trial with an Historical Control Group.

Abstract

Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus-6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial we investigated the effects of prophylactic foscarnet (90 mg/kg i.v. infusion from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6 encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients. Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis group. Outcomes were compared with an historical control group who received CBT between 2010 and 2014 (standard-treatment group, n = 63). The cumulative incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA ≥ 104 copies/mL, at 60 days after CBT was significantly lower in the foscarnet-prophylaxis group than in the standard-treatment group (18.3% versus 57.3%, P < .001). Multivariate analysis revealed that myeloablative preconditioning and standard treatment were significant risk factors for high-level HHV-6 reactivation. The cumulative incidence of HHV-6 encephalitis at 60 days after CBT was not different between the groups (foscarnet-prophylaxis group, 12.4%; standard-treatment group, 4.9%; P = .14). The cumulative incidences of grades II to IV and grades III to IV aGVHD at 60 days after CBT were not different between the groups (grades II to IV aGVHD: foscarnet-prophylaxis group, 42.0%; standard-treatment group, 40.5%; P = .96; grades III to IV aGVHD: foscarnet-prophylaxis group, 14.5%; standard-treatment group, 14.5%; P = 1.00). In the setting of this study foscarnet significantly suppressed systemic HHV-6 reactivation in CBT recipients but failed to prevent the development of HHV-6 encephalitis. Suppression of HHV-6 reactivation by foscarnet did not show any effects against the incidence of aGVHD.

• Authors: Masao Ogata, Kuniko Takano, Yukiyoshi Moriuchi, Tadakazu Kondo, Toshimitsu Ueki, Nobuaki Nakano, Takehiko Mori, Nobuhiko Uoshima, Koji Nagafuji, Satoshi Yamasaki, Yasuhiko Shibasaki, Rika Sakai, Koji Kato, Ilseung Choi, Yumi Jo, Tetsuya Eto, Shinichi Kako, Kumi Oshima, Takahiro Fukuda
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 24 Issue 6 Pg. 1264-1273 (06 2018) ISSN: 1523-6536 [Electronic] United States
• PMID: 29454651 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antiviral Agents
• DNA, Viral
• Myeloablative Agonists
• Foscarnet

Topics

• Adolescent
• Adult
• Aged
• Antiviral Agents (pharmacology, therapeutic use)
• DNA, Viral (blood)
• Encephalitis, Viral (drug therapy, prevention & control)
• Female
• Fetal Blood (transplantation)
• Foscarnet (pharmacology, therapeutic use)
• Graft vs Host Disease
• Herpesvirus 6, Human (drug effects)
• Historically Controlled Study
• Humans
• Middle Aged
• Myeloablative Agonists (pharmacology)
• Premedication (methods)
• Prospective Studies
• Risk Factors
• Treatment Outcome
• Virus Activation (drug effects)
• Young Adult